title: Treatment of lung cancer patients and concomitant use of drugs interacting with cytochrome P450 isoenzymes.
abstract: OBJECTIVE
  The majority of anticancer medicines used in the therapy of lung cancer patients are metabolized by cytochrome P450 (CYP450) enzymes, but little is known about the frequency of prescribed concomitant medicines interacting via the same enzyme system. This study analyzed the use of medications that could cause drug-drug interactions (inhibition or induction) in lung cancer patients before and during anticancer treatment.
  
  
  METHODS
  In this retrospective cross sectional study, all lung cancer patients (ICD-9 codes 162.2-162.9, 231.2) aged ≥18 years who received any anticancer medicines between 1/1/2004 and 6/30/2008 were identified in the US Thomson Reuters MarketScan(®) Claims Database. Patients had to have data for at least 12 months prior to (pre-period) and during their treatment, had no other cancer or use of other anticancer treatment in the pre-period. Patients with renal disease, renal failure, or liver failure were excluded. Drugs known to induce or inhibit P450 enzymes and used before and during lung cancer treatment were categorized with respect to their potency (strong, moderate, low).
  
  
  RESULTS
  Out of 144,959 lung cancer patients, 6647 (4.6%) patients met the study entry criteria. Mean age was 67 years, 53% were men, and mean Charlson combordity index was 3.5. 99% of patients received at least one drug known as a substrate, inhibitor or inducer of P450 (98% inhibitors, 93% inducers, 98% substrates) during the patient's anticancer treatment episode. Mean co-treatment duration with any CYP450 agent was 99 days (76% of the episode length); ≥2 different CYP450 agents were prescribed during 98% of episodes, and ≥10 different CYP450 agents were prescribed during 44% of episodes. Use of CYP450 agents was similar in the pre-treatment period: at least one CYP450 agent was prescribed during 99% of episodes (99% inhibitors, 79% inducers, 98% substrates).
  
  
  CONCLUSIONS
  Drugs which may cause drug-drug interactions while affecting the CYP 450 enzymes are frequently prescribed both before and during anticancer treatment of lung cancer patients.
authors.affiliation: Thomson Reuters, Cambridge, MA 02140, USA. xue.song@thomsonreuters.com
authors.forename: Xue
authors.initials: X
authors.lastname: Song
authors.forename: Helen
authors.initials: H
authors.lastname: Varker
authors.forename: Michel
authors.initials: M
authors.lastname: Eichelbaum
authors.forename: Peter
authors.initials: P
authors.lastname: Stopfer
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shahidi
authors.forename: Kathleen
authors.initials: K
authors.lastname: Wilson
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaiser
authors.forename: Henrik W
authors.initials: HW
authors.lastname: Finnern
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D000077143:Docetaxel; D004347:Drug Interactions; D004790:Enzyme Induction; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009325:Nausea / Q000209:etiology; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D014748:Vinca Alkaloids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D014839:Vomiting / Q000209:etiology
chemical_list: D043823:Taxoids; D014748:Vinca Alkaloids; D000077143:Docetaxel; D003577:Cytochrome P-450 Enzyme System